1. A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis
- Author
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Brad H. Rovin, Neil Solomons, William F. Pendergraft, Mary Anne Dooley, James Tumlin, Juanita Romero-Diaz, Lidia Lysenko, Sandra V. Navarra, Robert B. Huizinga, Ihar Adzerikho, Elena Mikhailova, Natalya Mitkovskaya, Sergey Pimanov, Nikolay Soroka, Boris Iliev Bogov, Boriana Deliyska, Valentin Ikonomov, Eduard Tilkiyan, Ruth Almeida, Fernando Jimenez, Faud Teran, Irma Tchokhonelidze, Nino Tsiskarishvili, Maynor Herrera Mendez, Nilmo Noel Chavez Perez, Arturo Reyes Loaeza, Sergio Ramon Gutierrez Urena, Juanita Romero Diaz, Rodolfo Araiza Casillas, Magdalena Madero Rovalo, Stanislaw Niemczyk, Antoni Sokalski, Andrzej Wiecek, Marian Klinger, Olga V. Bugrova, Tatiana M. Chernykh, Tatiana R. Kameneva, Lidia V. Lysenko, Tatiana A. Raskina, Olga V. ReshEtko, Natalia N. Vezikova, Tatiana V. Kropotina, Adelya N. Maksudova, Vyacheslav Marasaev, Vladimir A. Dobronravov, Ivan Gordeev, Ashot M. EssAian, Alexey Frolov, Rosa Jelacic, Dragan Jovanovic, Branka Mitic, Gordana Pekovic, Milan Radovic, Goran Radunovic, Patricia Carreira, Federico Diaz Gonzalez, Xavier Fulladosa, Eduardo Ucar, Shamila De Silva, Chula Herath, Anura Hewageegana, Abdul Latiff Mohamed Nazar, A.W.M. Wazil, Iryna Dudar, Olga Godlevska, Svitlana Korneyeva, ViktoriIa Vasylets, Nataliya Sydor, Mykola Kolesnyk, Samir V. Parikh, Nancy Olsen, Ellen M. Ginzler, James A. Tumlin, Amit Saxena, Ramesh Saxena, Richard Alan Lafayette, William Franklin Pendergraft, Amber S. Podoll, Annie A. Arrey-Mensah, Michael Bubb, Jennifer Grossman, Alejandro I. Oporta, Alireza Nami, Md. Mujibur Rahman, Syed Atiqul Haq, Tak Mao Daniel Chan, Mok Mo Yin Temy, Harold Michael P. Gomez, James Bermas, Bernadette Heizel Reyes, Llewellyn T. Hao, Linda Charmaine Roberto, Eric Amante, Allan E. Lanzon, Jung-Yoon Choe, Tae Young Kang, Yon Su Kim, Seung-Geun Lee, Ji Soo Lee, Jason Choo Chon Jun, Archana Vasudevan, Shue-Fen Luo, Tien-Tsai Cheng, Bancha Satirapoj, and Kajohnsak Noppakun
- Subjects
0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Calcineurin Inhibitors ,030232 urology & nephrology ,Lupus nephritis ,Placebo ,Mycophenolate ,Gastroenterology ,Drug Administration Schedule ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Double-Blind Method ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Adverse effect ,Glucocorticoids ,Proteinuria ,Dose-Response Relationship, Drug ,business.industry ,Remission Induction ,Mycophenolic Acid ,medicine.disease ,Lupus Nephritis ,Voclosporin ,Calcineurin ,030104 developmental biology ,Treatment Outcome ,chemistry ,Nephrology ,Cyclosporine ,Drug Therapy, Combination ,Female ,medicine.symptom ,business ,Immunosuppressive Agents - Abstract
Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.
- Published
- 2018